Events at the cell surface are critical in the control of cell growth of normal and neoplastic cells and in cell-cell recognition. There is increasing evidence that surface functions are controlled or modified by cytoplasmic microtubules (MT) and microfilaments (MF). The mechanism by which MT and MF interact with the cell membrane is largely unknown. In large part this is due to the difficulty of analyzing complex dynamic systems involving membranes, MF and MT and in understanding the formation of MT and MF from their protein subunits. We have now developed an approach based on resonance energy transfer between separately labelled MT or MF which permits study of MT or MF polymerization and binding to membranes. The proposed study has three broad aims: one, to study the polymerizations of tubulin and actin and their interaction; to determine if there is specific binding of actin filaments or MT to membranes and to analyze their number and affinity; and, three, to determine the distribution of bound lectins on intact cells. Resonance energy transfer enables each of these problems to be approached in a unique fashion. In the latter case for example a kind of topographical map of the surface can be constructed. Membrane binding can be examined under conditions in which MT or MF binding is induced in intact cells, for example by binding lectins to the surface. The effects of neoplastic transformation and treatments with drugs such as cyclic AMP or cyclic GMP which modify behavior on membrane-MF, MT interactions can be examined. These studies provide a basis for a new approach to the study of how MT and MF determine surface function and cell behavior. BIBLIOGRAPHIC REFERENCES: Oliver, J. M. Krawiec, J. A., and Berlin, R. D. Carbamylcholine prevents giant granule formation in cultured fibroblasts from beige (Chediak-Higashi) mice. J. Cell Biol. 69, 205 (1976). Berlin, R. D. and Oliver, J. M. Macrophage membranes, Chap. 10 in Immunobiology of the Macrophage, (Ed., D. S. Nelson, Academic Press) (1976).